Dry Eye SyndromePhase 2NCT01387347
Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye
A Phase 2 study testing Thymosin beta 4 in people with Dry Eye Syndrome and Dry Eye, run by ReGenTree, LLC.
Trial summary
Thymosin Beta 4 (Tβ4) is a synthetic copy of the naturally-occurring 43-amino acid peptide that is found in a variety of tissues. Tβ4 promotes/accelerates wound repair in dermal, ocular, and cardiac animal models. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Dry Eye Syndrome, Dry Eye
- What is being tested?
- Thymosin beta 4
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- Aug 2011to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have given a written, informed consent.
- Be able and willing to follow instructions, including participation in study assessments, and be present for the required study visits for the duration of the study.
- Have a best corrected visual acuity.
- Have a patient-reported history of dry eye in both eyes.
- Use and/or desire to use an artificial tear substitute for dry eye symptoms within the past 6 months.
- A negative urine pregnancy test if female of childbearing potential.
- Have a corneal fluorescein staining score of ≥ 2 in any corneal surface segment in at least one eye at Visit 1.
- -
Who cannot join
- Have contraindications to the use of the study drug.
- Have known allergy or sensitivity to the study drug or components thereof.
- Have anterior blepharitis.
- Be diagnosed with an on-going ocular infection or active ocular inflammation.
- Use contact lenses within 1 week before Visit 1 or during the course of the study.
- Have previously had Laser-Assisted in Situ Keratomileusis (LASIK) surgery within 12 months prior to Visit 1.
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- Be currently taking any topical ophthalmic prescription or over-the-counter (OTC) solutions, artificial tears, gels, or scrubs and cannot discontinue these medications for the duration of the trial.
- Have used topical ocular cyclosporine within 30 days prior to Visit 1.
- Have had a past or present evidence of malignancy.
About this study
Official title: A Double-Masked, Randomized, Single-Center Study Evaluating the Safety and Efficacy of 0.1% Tβ4 Ophthalmic Solution Compared to Vehicle on the Signs and Symptoms of Dry Eye in the Controlled Adverse Environment (CAE) Model
Thymosin Beta 4 (Tβ4) is a synthetic copy of the naturally-occurring 43-amino acid peptide that is found in a variety of tissues. Tβ4 promotes/accelerates wound repair in dermal, ocular, and cardiac animal models. Two recent pre-clinical evaluations have demonstrated that Tβ4 promotes corneal ocular surface defects healing in animal models of dry eye. RGN-259 (formulation of Tβ4 ophthalmic solution) mechanism of action offers potential to be a product that meets a major unmet medical need in patients with dry eye.
Read the detailed description
Tβ4 promotes wound repair and regeneration in various tissues. In the eye, it promotes corneal epithelial cell migration, decreases inflammation and has anti-apoptotic activities. It up-regulates the gene expression of laminin-5, a major subepithelial adhesion protein, located in the basement membrane region of the cornea, conjunctiva, and important in wound healing. In compassionate-use cases, Tβ4 has demonstrated efficacy in repairing non-healing neurotrophic corneal ulcers and other corneal epithelial wounds. In twenty-four nonclinical toxicology and safety pharmacology studies, the safety of Tβ4 has been demonstrated for its current and planned uses in man. The results of the two recent dry eye murine mouse model studies show that Tβ4 reduced corneal staining more than positive controls and demonstrated statistically significant reduction in staining compared to vehicle control. The results of these studies, in addition to data from compassionate use studies in patients with non-healing corneal surface defects, suggests that Tβ4 has a significant potential to be an important new safe and effective therapeutic in the treatment of dry eye syndrome.
- Conditions
- Dry Eye Syndrome, Dry Eye
- Being tested
- Thymosin beta 4, Placebo
- Keywords
- Thymosin beta 4, Dry eye syndrome, Dry eye
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thymosin beta 4Drug
Also called Tβ4, RGN-259 (eye drop formulation of Tβ4)
A preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days.
PlaceboDrug
Also called Vehicle Control
A preservative-free, sterile eye drop solution containing 0.0% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Thymosin Beta 4 | Active comparator | RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 Receives: Drug: Thymosin beta 4 |
| Placebo | Placebo comparator | The placebo solution is composed of the same excipients as RGN-259 but does not contain Tβ4. The Placebo is identical to the RGN-259 eye drops in color, consistency, and odor. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corneal Staining (Inferior Region) in the Worst Eye in the Controlled Adverse Environment (CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye
This is a test that uses orange dye (fluorescein) and a blue light to detect ocular surface defects associated with dry eye. If the test result is normal, the dye remains in the tear film on the surface of the eye and does not adhere to the eye itself. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29. The scale used to determine the difference in corneal fluorescein staining between RGN-259 and placebo is the ORA scale: 0= no staining (no detectable ocular defect)to 4= confluent staining( severe ocular defect).
Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes were equal at Visit 2, then the right eye was chosen as the worst eye.
Measured: Day 29 (end of treatment)
Ocular Discomfort in the Worst Eye in the Controlled Adverse Environment(CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye.
Dry eye causes ocular discomfort, which is measured using a validated 4-point ORA Scale from the start of the dosing till the end of treatment (Day 29). 0 = no discomfort to 4 = constant discomfort.
If the measurement is lower, then improvement of ocular discomfort can be inferred. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29.
Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes had were equal at Visit 2, then the right eye was chosen as the worst eye.
Measured: Day 29 (end of treatment)
Secondary outcomes (1)
Number of Adverse Events as a Measure of Safety and Tolerability
The Adverse events, which will be followed, are: impairment of visual acuity, an increase in intraocular pressure (IOP), and an increase in corneal sensitivity in both eyes.
Measured: Throughout the study till Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionOct 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Dry Eye SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReGenTree, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ORA, Inc.
- Responsible party
- Sponsor
- Investigators
- Gail Torkildsen, MD, Principal investigator, Ora Clinical Research and Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01387347
- Sponsor's protocol ID
- RGN-DE-202
- Status last verified
- Dec 2012
- First submitted
- 29 Jun 2011
- Last updated
- 10 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Masked, Randomized, Single-Center Study Evaluating the Safety and Efficacy of 0.1% Tβ4 Ophthalmic Solution Compared to Vehicle on the Signs and Symptoms of Dry Eye in the Controlled Adverse Environment (CAE) Model
- ClinicalTrials.gov ID
- NCT01387347
- Acronym / sponsor ID
- RGN-DE-202
- Conditions
- Dry Eye Syndrome, Dry Eye
- Keywords
- Thymosin beta 4, Dry eye syndrome, Dry eye
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- ReGenTree, LLCIndustry (pharma, biotech, devices)
- Collaborators
- ORA, Inc.
- Study start
- Aug 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 4 Jul 2011 (estimated)
- Results
- Posted 24 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thymosin Beta 4 (Tβ4) is a synthetic copy of the naturally-occurring 43-amino acid peptide that is found in a variety of tissues. Tβ4 promotes/accelerates wound repair in dermal, ocular, and cardiac animal models. Two recent pre-clinical evaluations have demonstrated that Tβ4 promotes corneal ocular surface defects healing in animal models of dry eye. RGN-259 (formulation of Tβ4 ophthalmic solution) mechanism of action offers potential to be a product that meets a major unmet medical need in patients with dry eye.
Detailed description
Tβ4 promotes wound repair and regeneration in various tissues. In the eye, it promotes corneal epithelial cell migration, decreases inflammation and has anti-apoptotic activities. It up-regulates the gene expression of laminin-5, a major subepithelial adhesion protein, located in the basement membrane region of the cornea, conjunctiva, and important in wound healing. In compassionate-use cases, Tβ4 has demonstrated efficacy in repairing non-healing neurotrophic corneal ulcers and other corneal epithelial wounds. In twenty-four nonclinical toxicology and safety pharmacology studies, the safety of Tβ4 has been demonstrated for its current and planned uses in man. The results of the two recent dry eye murine mouse model studies show that Tβ4 reduced corneal staining more than positive controls and demonstrated statistically significant reduction in staining compared to vehicle control. The results of these studies, in addition to data from compassionate use studies in patients with non-healing corneal surface defects, suggests that Tβ4 has a significant potential to be an important new safe and effective therapeutic in the treatment of dry eye syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thymosin Beta 4 | Active comparator | Drug: Thymosin beta 4RGN-259 is a preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo solution is composed of the same excipients as RGN-259 but does not contain Tβ4. The Placebo is identical to the RGN-259 eye drops in color, consistency, and odor. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Have given a written, informed consent.
- Be able and willing to follow instructions, including participation in study assessments, and be present for the required study visits for the duration of the study.
- Have a best corrected visual acuity.
- Have a patient-reported history of dry eye in both eyes.
- Use and/or desire to use an artificial tear substitute for dry eye symptoms within the past 6 months.
Key exclusion criteria (9 listed)
- Have contraindications to the use of the study drug.
- Have known allergy or sensitivity to the study drug or components thereof.
- Have anterior blepharitis.
- Be diagnosed with an on-going ocular infection or active ocular inflammation.
- Use contact lenses within 1 week before Visit 1 or during the course of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thymosin beta 4Also: Tβ4, RGN-259 (eye drop formulation of Tβ4)A preservative-free, sterile eye drop solution containing 0.1% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days. | Drug | Thymosin Beta 4 |
| PlaceboAlso: Vehicle ControlA preservative-free, sterile eye drop solution containing 0.0% (w/w) Tβ4 for direct instillation into each eye, twice a day (BID) for 28 days. | Drug | Placebo |
Primary outcome
Corneal Staining (Inferior Region) in the Worst Eye in the Controlled Adverse Environment (CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye
Time frame: Day 29 (end of treatment)
This is a test that uses orange dye (fluorescein) and a blue light to detect ocular surface defects associated with dry eye. If the test result is normal, the dye remains in the tear film on the surface of the eye and does not adhere to the eye itself. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29. The scale used to determine the difference in corneal fluorescein staining between RGN-259 and placebo is the ORA scale: 0= no staining (no detectable ocular defect)to 4= confluent staining( severe ocular defect). Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes were equal at Visit 2, then the right eye was chosen as the worst eye.
Ocular Discomfort in the Worst Eye in the Controlled Adverse Environment(CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye.
Time frame: Day 29 (end of treatment)
Dry eye causes ocular discomfort, which is measured using a validated 4-point ORA Scale from the start of the dosing till the end of treatment (Day 29). 0 = no discomfort to 4 = constant discomfort. If the measurement is lower, then improvement of ocular discomfort can be inferred. The test is carried out throughout the study till end of treatment Day 29. However, the primary outcome measure itself is determined on Day 29. Worst eye: In the case that both eyes were eligible for analysis, the worst eye was chosen as the eye with the greater increase of inferior corneal staining from Visit 1 to Visit 2. If both eyes were equal, the eye with greater ocular discomfort at Visit 2 was chosen as the worst eye. If both eyes had were equal at Visit 2, then the right eye was chosen as the worst eye.
1 secondary outcome
Number of Adverse Events as a Measure of Safety and Tolerability
Time frame: Throughout the study till Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail Torkildsen, MD principal investigator
Ora Clinical Research and Development
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Thymosin beta 4 in people with Dry Eye Syndrome and Dry Eye, run by ReGenTree, LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corneal Staining (Inferior Region) in the Worst Eye in the Controlled Adverse Environment (CAE) Model, Which is a Regulated Environmental Setting Aimed at Exacerbating the Signs and Symptoms of Dry Eye (time frame: Day 29 (end of treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2015.